In order to understand better the biochemical control and regulation of epidermal proliferation, we have continued our inquiry into the sequence of cellular events during epidermal proliferation and differentiation. We have pursued three major problems: 1. The isolation and purification of an active epidermal chalone fraction. 2. Cell to cell communication in epidermal tissue and the cellular events associated with epidermal hyperplasia. 3. How cell to cell communication in epidermal tissue is influenced by compounds acting at the cell membrane. We have found that epidermal stripping will stimulate basal cells in G0 or G1 to S phase in their cell cycle. The biochemical events associated with stimulation have many similarities to the events in normal homeostasis and those resulting from wounds, chemical carcinogens, radiation trauma. By use of our in vivo and in vitro techniques, our experiments will attempt to obtain a clearer explanation of the biochemical events accompanying epidermal stripping and/or enzyme induction with epidermal hyperplasia. These investigations will aid in obtaining an insight of cell to cell communication in the epidermis; from the transmission of the original signal (after stripping) to its translation at the cell membrane (cell surface receptor sites) and the cell nucleus which result in a stimulation of thymidine incorporation into DNA. Additional inquiry will be made as to how compounds that influence the adenyl cyclase system react with the stimulus signal. BIBLIOGRAPHIC REFERENCES: Rothberg, S. and Arp, B.C.: Inhibition of epidermal and dermal DNA synthesis by mouse and cow-snout epidermal extracts. J. Invest. Derm. 64, 245 (1975). Rothberg, S., Nancarrow, G.E., Meydrech, E.F., Iwanik, M.J.: Extracellular influence on epidermal DNA synthesis. Fed. Proc. Absts. 34, 704 (1975).